Conventionally, in chemical screening using a biological sample (represented by a cell), the action of a cell is monitored by fluorochrome method or a micropipette electrode method to evaluate the action and effect of a drug for the cell.
Fluorochrome methods are methods for optically measuring, using fluorochromes which specifically react with various ion concentrations and a membrane-potential-sensitive fluorochrome, the action of a cell which is influenced by a drug, i.e., the degree of change in fluorescence of the cell according to changes in the membrane potential and ion concentration of the cell. In fluorochrome methods, the step of staining a cell with a dye is necessary. Therefore, influence of a dye to a cell can not be eliminated. Moreover, in fluorochrome methods, fluorescence from a fluorochrome is weakened with time, so that detection accuracy becomes poor. This is a weak point of fluorochrome methods.
On the other hand, micropipette electrode methods are of a method for directly measuring an electrical action of a cell, such as an intracellular potential, a current flowing through an ion channel existing in a cell membrane, a current flowing through a channel activated by a drug receptor. Therefore, with the micropipette electrode method, more detail and wider range of information about the action of a cell which is influenced by a drug can be obtained. The micropipette electrode method is a very useful method for obtaining information about the action of a cell.
In general, in an intracellular potential recording method that is one of micropipette electrode methods, a micropipette formed by stretching thermally-melt quartz glass or borosilicate glass so as to have a submicron tip diameter is inserted into a cell. Moreover, in a patch clamp method that is one of micropipette electrode methods, to locally measure a very small region of about 0.1-20 micron in the cell, a micropipette is pressed against a cell membrane so that the micropipette and the membrane are attached to each other at a predetermined angle.
Problems to be Solved
However, in a known micropipette electrode method, a technician operates a micropipette, relying on a micrograph, to insert a micropipette into a cell fixed onto a substrate, or attach a micropipette to the cell. Therefore, a highly accurate micropipette position controller is needed, and furthermore, a skill to insert a micropipette into a cell or attach a micropipette to a cell is needed.
Accordingly, the micropipette electrode methods are not suitable as a technique for screening a large amount of compounds as candidates for drugs at high speed.
In Japanese Laid-Open Patent Publication 9-289886, a cell membrane potential detector for use in a micropipette electrode method is disclosed. The cell membrane potential detector includes a protruding electrode for cell insertion, which is provided on a bottom face of a dish having a plurality of with bottom holes and serves as a micropipette, and a reference electrode provided in a side surface of each of the with bottom holes.
The cell membrane potential detector disclosed in the publication does not include means for accurately leading a cell to the protruding electrode. Therefore, a skill of a technician is needed to lead a cell to a protruding electrode.
In view of the above-described problems, the present invention has been devised to provide a measurement device which allows electrophysiological measurement of a biological sample to be performed in a simple, accurate, high-speed and automatic manner.